He started his legal career in 1974 as an apprentice "solicitor with the firm James Campbell & Co. On qualifying in 1976 he became an assistant solicitor with Ross, Harper and Murphy, and was promoted to partner in 1980. He became a partner in McCluskey Browne in 1985 and a council member of the "Law Society of Scotland 1988-1992. He was admitted as an "advocate in 1993, practising at the Scottish bar until 1997. He worked mainly in child law.

In a free parliamentary vote on 20 May 2008, Browne voted for cutting the upper limit for abortions from 24 to 12 weeks, along with two other Catholic cabinet ministers "Ruth Kelly and "Paul Murphy.[6] He returned to the backbenches in October 2008 following a cabinet reshuffle.

Browne is vice chairman of the Washington, DC-based Nuclear Threat Initiative, a non-profit, nonpartisan organization founded in 2001 by former U.S. Senator Sam Nunn, who serves as co-chair and CEO, and CNN founder and philanthropist Ted Turner. NTI’s mission is to strengthen global security by reducing the risk of use and preventing the spread of nuclear, biological and chemical weapons.

Des Browne is a signatory of "Global Zero (campaign), a non-profit international initiative for the elimination of all nuclear weapons worldwide.[10] Since its launch in Paris in December 2008,[11] "Global Zero (campaign) has grown to 300 leaders, including current and former heads of state, national security officials and military commanders, and 400,000 citizens worldwide; developed a practical step-by-step plan to eliminate nuclear weapons; launched an international student campaign with 75 campus chapters in eight countries; and produced an acclaimed documentary film, "Countdown to Zero, in partnership with "Lawrence Bender and "Participant Media.[12]

In February 2009, Browne was appointed by PM Brown as the government's "special envoy to "Sri Lanka. However, the government of "Mahinda Rajapaksa, fighting the "LTTE rebel group, rejected Browne's appointment, stating that the British government made the appointment unilaterally, without consultation with the Sri Lankan government.[13]